Research Projects

Synthetic polymers are emerging as indispensable components in biomedical research and they cater wide range of biomedical applications including drug delivery in cancer research. Among many vital requirements, biocompatible, biodegradable and bio-resource based synthetic macromolecules are essential prerequisites for long-term impact with minimum or no side effects under physiological conditions. Synthetic polypeptides based on natural α-amino acids mimic protein-like assemblies for both fundamental understanding and new technology development. Polypeptides are typically produced via the ring opening polymerization (ROP) of 5-member N-carboxy anhydrides (NCA) of -amino acid natural resources. This technology has been predominantly reported (nearly 98 % of the literature) for -helical polypeptides due to their excellent solubility in the organic solvents to carry out the polymerization in homogeneous phase, easy structural characterization and molecular weight determination and so on so forth. On the contrary, -Sheet forming polypeptides are one of the least explored synthetic systems and this main restriction associated with the uncontrollable-precipitation of the polymer chains during their synthesis. As a consequence, accomplishing complete control over the “livingness in -sheet polypeptides” and expansion of the propagating polymer chains for building many unexplored polypeptide block copolymer macromolecular architectures was still a distant dream for synthetic polymer chemist. This unresolved problem was recently addressed by us via carefully developing “steric-ROP” strategy to build high molecular weight -sheet polypeptides (Rahul and Jayakannan, Biomacromolecules, 2022, 23, 2667–2684.). In this process, the propagating polypeptide chains undergo conformational transition from -sheet to α-helix to produce freely soluble polymers along with excellent “living ROP polymerization” characteristics. Post-polymerization de-protection strategy was employed to restore the -sheet polypeptides as and when required. The current research proposal is aimed to design new classes of β-sheet polypeptides based on poly(ʟ-serine), poly(ʟ-cysteine), poly(ʟ-tyrosine) and poly(ʟ-threonine)s and further expand the synthetic methodology to their unexplored polypeptide block copolymers which are completely new entity in the literature. Further, our group’s 15 years expertise in cancer research will be explored to study the drug delivery aspects of functional β-sheet polypeptide block copolymers for delivering clinical anticancer drugs and NIR biomarkers both in vitro and in vivo in mice models. Developing β-sheet polypeptides having their original functional groups (-OH, SH and phenolic-OH) are very crucial for their extended biological activity and exploit the natural selection of these functionality in synthetic mimics to generate new knowledge and biomaterials for long-term impact of polymer technology in biomedical applications.

Polypeptides, Drug Delivery, Biodegradable Polymers, Block copolymers, Polymer nano-assemblies, Cancer research